20-17969694-T-G

Position:

• chr20-17969694-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_052865.4(MGME1):​c.-59-107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 677,250 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (32 hom., cov: 33)
  • Exomes 𝑓: 0.019 (124 hom.)
• Consequence: MGME1 NM_052865.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.120

Genes affected

MGME1 (HGNC:16205): (mitochondrial genome maintenance exonuclease 1) The protein encoded by this gene is a nuclear-encoded mitochondrial protein necessary for the maintenance of mitochondrial genome synthesis. The encoded protein is a RecB-type exonuclease and primarily cleaves single-stranded DNA. Defects in this gene have been associated with mitochondrial DNA depletion syndrome-11. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

OVOL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-17969694-T-G is Benign according to our data. Variant chr20-17969694-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1196344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0161 (2456/152298) while in subpopulation AMR AF= 0.0285 (435/15286). AF 95% confidence interval is 0.0263. There are 32 homozygotes in gnomad4. There are 1180 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGME1	NM_052865.4	c.-59-107T>G		intron_variant		ENST00000377710.10	NP_443097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGME1	ENST00000377710.10	c.-59-107T>G		intron_variant		1	NM_052865.4	ENSP00000366939.5
MGME1	ENST00000377709.1	c.-59-107T>G		intron_variant		2		ENSP00000366938.1
MGME1	ENST00000377704.4	c.-59-107T>G		intron_variant		3		ENSP00000366933.4
OVOL2	ENST00000486776.5	n.492-12657A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2456 AN: 152180 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.0193 AC: 10121 AN: 524952 Hom.: 124 AF XY: 0.0192 AC XY: 5184 AN XY: 270684

Gnomad4 AFR exome AF: 0.00316

Gnomad4 AMR exome AF: 0.0192

Gnomad4 ASJ exome AF: 0.0222

Gnomad4 EAS exome AF: 0.0000674

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.0106

Gnomad4 NFE exome AF: 0.0230

Gnomad4 OTH exome AF: 0.0182

GnomAD4 genome AF: 0.0161 AC: 2456 AN: 152298 Hom.: 32 Cov.: 33 AF XY: 0.0158 AC XY: 1180 AN XY: 74468

Gnomad4 AFR AF: 0.00392

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0204

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0229

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0172 Hom.: 5

Bravo AF: 0.0168

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142001430; hg19: chr20-17950337;